The role of
serotonin (5-hydroxytryptamine) in appetite control is long established. Serotonergic manipulations reduce food intake in rodents in a manner consistent with satiety. In humans, drugs such as
fenfluramine,
dexfenfluramine and
sibutramine all reduce energy intake, suppress hunger and enhance satiety. Effects on eating behaviour and subjective sensations of appetite are associated with the
weight loss-inducing effects of these treatments. Currently, no appetite-suppressing drugs are approved specifically for the treatment of
obesity. However, a new generation of
serotonergic drugs have progressed through clinical development. The
serotonin 5-HT(2C)-receptor selective agonist
lorcaserin, a
drug specifically developed to target satiety without producing the side effect profiles of its predecessors, has been shown to significantly reduce energy intake and
body weight. The
weight loss produced by
lorcaserin appears modest, and behavioural effects, particularly its supposed satiety-enhancing effects, have yet to be characterized. The monoaminergic re-uptake inhibitor
tesofensine has also been shown to produce impressive
weight loss in smaller-scale clinical studies. It remains unclear if this
drug produces any effects on appetite mediated by
serotonin, or whether
weight loss is produced largely through enhanced energy expenditure. Evidence indicates that
tesofensine strengthens satiety, but behavioural specificity and psychological side effects remain an issue. The serotonergic system remains a viable target for anti-
obesity treatment. In this review, we examine the limited behavioural data available on these two new CNS-acting
appetite suppressants.